Can You Slow The Aging Process?

A Holistic Approach To Living Healthy Longer

Author: Dr. Stephen Chaney 

Fountain Of YouthEver since Ponce de Leon’s famed 1513 expedition, people have been searching for the proverbial “Fountain of Youth”.

There have been hucksters selling pills and potions to reverse the aging process. Most of them didn’t work. They were no better than snake oil.

There have been legitimate scientists investigating the effect of supplements, diets, and lifestyle on the aging process. Most of these studies have come up empty.

In this study (M Gagesch et al, Journal of Frailty And Aging, 12: 71-77, 2023) the authors hypothesized that a holistic approach might be better than individual interventions. They asked whether a combination of vitamin D3 supplementation, omega-3 supplementation, and exercise might be more effective at slowing the aging process than any one of them alone.

There was good reason for choosing each of these interventions:

  • Low 25-hydroxyvitamin D levels have been associated with frailty in several studies. But association studies do not prove cause and effect, and no randomized, placebo control studies have measured the effect of vitamin D supplementation on frailty.
  • Omega-3 fatty acids have been linked to skeletal muscle health, and some studies have suggested omega-3 supplementation may improve muscle function in older adults.
  • A recent study has reported that a supervised exercise program reduced frailty in older adults. The authors wanted to see if the same was true for unsupervised, at-home exercise program.

How Was This Study Done?

clinical studyThe data from this study were collected as part of the DO-HEALTH study, a 3-year, double-blind, randomized, placebo-controlled clinical trial designed to identify interventions that support healthy aging in European adults aged 70 and older.

Initially, 2,157 healthy, community-dwelling adults were enrolled from five countries (Switzerland, Germany, Austria, France, and Portugal). They were examined in clinical centers at the beginning of the study and years 1, 2, and 3, with phone follow-up at 3-month intervals.

Aging was measured by something called the frailty index. At each clinic visit the participants were evaluated in five areas:

  1. Weakness was measured as grip strength. Weakness was defined as being in the lowest quintile of grip strength for someone their age and gender.

2) Fatigue was defined as a positive answer to the question, “In the last month have you had too little energy to do the things you wanted to do?”

3) Involuntary weight loss was defined as >5% weight loss within a year.

4) Low gait speed was defined as <2 ft/sec walking speed.

5) Low activity level was defined as a response of, “Less than once a week” to the question, “How often do you engage in activities that require a low or moderate level of energy such as gardening, cleaning the car, or going on a walk?”

    • Participants with 0 positive items were classified as robust.
    • Those with 1 or 2 positive items were classified as pre-frail.
    • Those with 3 or more positive items were classified as frail.

Only those participants from the DO-HEALTH study classified as robust at the first clinical visit (1,137 participants) were included in this study. The study measured how many of them became pre-frail or frail during the average follow-up of 2.9 years.

The interventions were:

  • Capsules containing a total of 2,000 IU/day of vitamin D3 with sunflower oil capsules as a placebo.
  • Capsules containing a total of 1,000 mg of EPA and DHA in a 1:2 ratio with a sunflower oil capsule as a placebo.
  • Exercise consisting of an unsupervised strength-training routine for 30 minutes, 3 times per week.
  • In this case the control was an unsupervised joint-flexibility routine for 30 minutes, 3 times per week.

The interventions were done individually, two together (vitamin D + omega-3, vitamin D + exercise, omega-3 + exercise), and all three together (vitamin D + omega-3 + exercise).

The results were corrected for age, sex, and low-trauma falls in the preceding 12 months.

Finally, the study measured blood 25-hydroxyvitamin D levels and omega-3 levels at each office visit. They found:

  • 28% of the participants were deficient in vitamin D at the beginning of the study.
  • The interventions gave the expected increase in vitamin D and omega-3 status.

Can You Slow The Aging Process?

Older Couple Running Along BeachAt the end of 3 years:

  • 61.2% of the participants had declined from robust health to the pre-frail category.
  • 2.6% of the participants had declined from robust health to the frail category.

[Note: The terms “pre-frail” and “frail” are measures of aging which I have described above.]

The number of participants in the frail category were too small to obtain a statistically significant measure of the effects of vitamin D, omega-3s, and exercise on frailty, so I will only discuss the results measuring their effect on pre-frailty in this review. These results are:

  • None of these interventions had a statistically significant effect on aging by themselves, as measured by the transition from robust health to pre-frailty.
  • None of these interventions had a statistically significant effect on aging when combined in pairs, although the vitamin D3-omega-3 pair came close to significance (31% reduction in pre-frailty with a probability of 94% (probabilities of 95% and above are considered significant.))
  • However, the combination of vitamin D3, omega-3s, and exercise reduced the risk of aging by 39%, which was statistically significant (96% probability).

The authors concluded, “Robust, generally healthy and active older adults without major comorbidities [diseases], may benefit from a combination of high-dose, supplemental vitamin D3, marine omega-3s, and SHEP [unsupervised strength training] with regard to the risk of becoming pre-frail over 3 years.”

A Holistic Approach To Living Healthy Longer

holistic approachThis study was a double-blind, placebo-controlled study, which is the gold standard for clinical studies. It was also unusually large (1,137 participants) and long (3 years) for this kind of study.

It was also much better than most double-blind, placebo-controlled studies in that it included three interventions (vitamin D3 supplementation, omega-3 supplementation, and exercise) and looked at their effect on aging individually, in pairs, and all three together.

One take-home lesson from this study was that a holistic approach that included all 3 interventions was superior to any one of these interventions alone or in pairs.

But the most important take-home lesson is this:

If you asked your doctor what you should do to slow the aging process, he or she would probably tell you, “Exercise may help, but forget supplementing with extra vitamin D or omega-3s. They have no proven benefits.”

They would be correct based on studies of each of these interventions individually. And the studies they might quote would be double-blind, placebo-controlled studies, the gold standard of clinical studies.

But would that be the best advice. Clearly not. The best advice would be to follow a holistic approach and use all 3 interventions together.

Unfortunately, this is true for most studies of supplementation. Supplements are tested individually, as if they were “magic bullets”. And most of these studies come up short. They fail to find a significant benefit of supplementation.

Supplements are almost never tested holistically in combination with each other and other interventions, but that’s where the “magic” really happens.

If you are a regular reader of “Health Tips From The Professor”, this should come as no surprise to you. I have often shared the Venn diagram on the upper left and said that the sweet spot is when two or more of these interventions overlap.

Of course, this is the first study of its kind. More studies are needed. More importantly, we need studies to fill in the other parts of the Venn diagram. We need to ask about the effect of diet and obesity on aging. For example:

  • If we add a healthy diet to vitamin D, omega-3s, and exercise, can we reduce aging even more dramatically?
  • Is the effort it takes to lose excess weight worth it? Does adding it to diet, supplementation, and exercise reduce the aging process even more?

Of course, I think the answer to those questions is an unequivocal, “Yes”. Multiple studies have shown that both a healthy weight and a healthy diet help you live healthier longer.

But I am a scientist. Neither diet nor weight loss have been tested in combination with supplementation and exercise. I would like to see studies combining all these modalities in a single double-blind, placebo-controlled experiment.

So, what does this mean for you? If you want to slow the aging process, if you are in search of your personal “Fountain of Youth…

  • This study suggests that vitamin D3 supplementation (2,000 IU/day), omega-3 supplementation (1,000 mg of EPA + DHA), and an exercise program that emphasizes strength training can help you slow the aging process.

But that is only the beginning. I also recommend…

  • Including a healthy diet and a healthy weight in your anti-aging regimen.
  • Making sure your diet has enough protein and leucine, since older adults need more of both to maximize the benefits of strength training.
  • Including other supplements as evidence for their benefit in slowing the aging process becomes available.

The Bottom Line 

A recent double-blind, placebo-controlled study looked at the effect of vitamin D3 supplementation (2,000 IU/day), omega-3 supplementation (1,000 mg/day EPA + DHA in a 1:2 ratio), and an unsupervised strength training program on the aging process.

It differed from most other double-blind, placebo-controlled studies in that:

  • It was larger (1,137 participants) and longer (3 years) than most.
  • More importantly, each intervention was tested individually, in pairs, and all 3 together.

The study found that:

  • None of these interventions had a statistically significant effect on aging by themselves.
  • None of these interventions had a statistically significant effect on aging when combined in pairs, although the vitamin D3-omega-3 pair came close to significance.
  • However, the combination of vitamin D3, omega-3s, and exercise reduced the risk of aging by a statistically significant 39%.

One take-home lesson from this study was that a holistic approach that included all 3 interventions was superior to any one of these interventions alone or in pairs.

But the most important take-home lesson is this:

If you asked your doctor what you should do to slow the aging process, he or she would probably tell you, “Exercise may help, but forget supplementing with extra vitamin D or omega-3s. They have no proven benefits.”

They would be correct based on studies of each of these interventions individually. And the studies they might quote would be double-blind, placebo-controlled studies, the gold standard of clinical studies.

But would that be the best advice? Clearly not. The best advice would be to follow a holistic approach and use all 3 interventions together.

Unfortunately, this is true for most studies of supplementation. Supplements are tested individually, as if they were “magic bullets”. And most of these studies come up short. They fail to find a significant benefit of supplementation.

Supplements are almost never tested holistically in combination with each other and other interventions, but that’s where the “magic” really happens.

For more information on this study and my recommendations on how to slow the aging process read the article above.

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure, or prevent any disease.

 ___________________________________________________________________________

My posts and “Health Tips From the Professor” articles carefully avoid claims about any brand of supplement or manufacturer of supplements. However, I am often asked by representatives of supplement companies if they can share them with their customers.

My answer is, “Yes, as long as you share only the article without any additions or alterations. In particular, you should avoid adding any mention of your company or your company’s products. If you were to do that, you could be making what the FTC and FDA consider a “misleading health claim” that could result in legal action against you and the company you represent.

For more detail about FTC regulations for health claims, see this link.

https://www.ftc.gov/business-guidance/resources/health-products-compliance-guidance

Can Tomatoes Be Engineered To Produce Vitamin D3?

The Good And Bad Of Genetically Modified Foods

Author: Dr. Stephen Chaney 

GM FruitsThe Floodgates have been opened. The USDA has just approved a genetically engineered purple tomato that contains the anthocyanins found in blueberries, blackberries, and eggplant. It could be appearing in your supermarkets as early as next spring.

And that is just the beginning. Several other genetically modified tomatoes are waiting in the wings. One example is a tomato that has been genetically engineered to produce vitamin D3 (J Li et al, Nature Plants, 8: 611-616, 2022).

“Why would you want that?”, you might ask. The rationale is simple:

  • And vitamin D insufficiency is not a trivial matter. In the words of the authors, in addition to bone health, vitamin D insufficiency “impacts immune function and inflammation and is associated with increased risk of…cancer, Parkinson’s disease, depression, neurocognitive decline, dementia, and the risk of coronavirus disease…”
  • Add to that the fact that tomatoes are grown and consumed in more than 170 countries worldwide. The authors felt that increasing the vitamin D content of tomatoes could be a simple and effective way to improve the vitamin D status of millions of people around the world.

In their own words, “We have developed a new dietary source of vitamin D in plants to meet the increasing demand for ways to address vitamin D insufficiency, which is of particular relevance to those adopting plant-rich, vegetarian or vegan diets.”

But is that true and is it safe? That is the topic of today’s health tip. But before I cover those topics, I should give you some background on vitamin D metabolism in humans and in plants.

Metabolism 101: Vitamin D Metabolism In Humans & Plants

7-dehydrocholesterol is the precursor to vitamin D3 in both humans and plants, but the amount of 7-dehydrocholesterol and the metabolic pathways producing it are very different.

Human Vitamin D3 Metabolism:

  • In humans, cholesterol is the precursor to 7-dehydrocholesterol. About 70% of cholesterol is synthesized by the liver, with the remaining 30% coming from our diet.
  • 7-dehydrocholesterol is synthesized from cholesterol in the epidermis (outer layer) of our skin. It is present in large amounts there but is present in only small amounts in the rest of the body.
  • UVB light is a component of sunlight, and UVB light drives the conversion of 7-dehydrocholesterol into vitamin D3 in our skin.

Plant Vitamin D3 Metabolism:

  • In plants, the pathway is reversed. 7-dehydrocholesterol is synthesized from other plant sterols. And 7-dehydrocholesterol is converted to cholesterol.
  • Cholesterol, in turn, is used to synthesize glycoalkaloid compounds that protect the plants from pests.
    • The gylcoalkaloids differ from plant to plant. In tomatoes the major ones are α-tomatine and esculeoside A and B.
    • α-tomatine and esculeoside A and B protect tomatoes from fungal, microbial, insect, and herbivoral attack.
  • Normally, 7-dehydrocholesterol and cholesterol present in very low amounts in plants because they are used to synthesize protective glycoalkaloid compounds.
  • UVB light is still required to convert 7-dehydrocholesterol to vitamin D3.

Can Tomatoes Be Engineered To Produce Vitamin D3?

Using modern genetic engineering techniques, the authors knocked out (deleted) the gene coding for the protein responsible for converting 7-dehydrocholesterol to cholesterol in tomatoes (shown as the red X in the figure above).

TomatoesIn the fruit:

  • 7-dehydrocholesterol levels are undetectable in ripe fruit of the wild-type tomato but were substantial in fruit of mutant tomatoes lacking the gene for converting 7-dehydrocholesterol to cholesterol.
  • As expected, levels of α-tomatine and esculeoside A and B were substantially lower in the fruit of mutant plants.
  • 7-dehydrocholesterol was evenly distributed in the skin and flesh of the fruit, which limited the ability of UVB light to convert all the 7-dehydrocholesterol to vitamin D3.
  • Even so, a one-hour exposure of the fruit to UVB light produced about 2 μg of vitamin D3 in a medium sized tomato.
    • That is equivalent to the vitamin D3 found in two eggs or 6 ounces of tuna, which are both recommended sources of vitamin D3.
    • The only non-fortified foods that are better sources of vitamin D3 are salmon and trout, which provide about 15 μg of vitamin D3 in a 3-ounce serving
  • The authors further speculated that the vitamin D3 content could be increased even more by:
    • Cutting the fruit into slices and air drying them in sunlight.
    • Removing the gene that produces UV-protecting chalcones in the skin of the fruit, thus allowing UVB light to penetrate further into the fruit. This is typical thinking by some of my scientific colleagues. If one mutation is good, two or more would be even better.

The authors concluded, “We have developed a new dietary source of vitamin D in plants to meet the increasing demand for ways to address vitamin D insufficiency”

In the leaves:

  • Qualitatively, the results were similar to those seen with the fruit.
    • 7-dehydrocholesterol levels were very low in the wild-type tomato but were substantially increased in the mutant tomatoes.
    • Levels of α-tomatine and esculeoside A and B were substantially lower in the leaves of the mutant plants.
  • Quantitatively, however, the results were different.
    • The amounts of 7-dehydrocholesterol were 300 to 600-fold higher in the leaves than in the ripe fruit.
    • The amount of vitamin D3 produced by a one-hour exposure to UVB light was 1,000-fold higher in the leaves than in the ripe fruit.
  • While people don’t eat the leaves of tomato plants, the authors visualized a different use for this material.
    • They envisioned using what would otherwise be waste vegetative material from growing tomatoes to produce vitamin D3 for vitamin D supplements.
    • This would be particularly beneficial for vegans because most vegan sources of vitamin D are vitamin D2, which is less effective than vitamin D3.

In the words of the authors, “The leaves of the mutant plants are rich sources of 7-dehydrocholesterol…[and could be used] for the manufacture of vitamin D3 supplements from plants that would be suitable for vegans…”

The Good And Bad Of Genetically Modified Foods

good news bad newsLike much else in today’s world of social media and online blogs and podcasts, both the benefits and risks of genetic engineering have been greatly exaggerated. I have discussed this topic at length in a previous issue  of “Health Tips From The Professor”.

On the one hand, my genetic engineering colleagues tend to focus on the genetic alteration that is beneficial and ignore other changes in the genetically altered food that could pose some risk.

  • I would be the first to admit that most of the risks are very small and unlikely to occur, but I think each potential risk should be thoroughly investigated before we release the genetically altered plant into the world.
  • As an analogy, I will use the story of Pandora’s Box. Pandora was given the box by an angry Greek God, who told her never to open it. But her curiosity got the beat of her. Once Pandora opened the box, she released sickness, death, and other evils into the world. And once they had been released, there was no way to get them back into the box. We don’t want to run this kind of risk with genetically altered plants.

On the other hand, there are the “Chicken Little’s” of the world who assume every potential risk is real and warn us that, “The sky is falling”. Most of the risks are theoretical only. They may never happen. I am just saying they should be examined before we release genetically altered plants into the wild.

In this article, I will try to avoid both extremes. I will put on my “sceptic’s hat” (Every good scientist keeps one of those in his or her closet) and carefully evaluate the benefits and the risks associated with using both the fruit and the leaves of this genetically altered tomato plant.

Tomato Fruit Engineered To Produce Vitamin D3

The Benefit:

The benefit is obvious. As the authors said, tomatoes are a widely consumed worldwide. The availability of an inexpensive plant source of vitamin D3 could go a long way towards improving vitamin D status in third world countries where vitamin D3 supplementation may not be practical.

SkepticMy Concerns:

  1. Are there health risks?
  • Most genetically engineered foods contain a protein sequence that is not found in the non-modified food. This raises the possibility of food allergies to the novel protein. The good news is that a protein has been removed in this mutant plant. There is no novel protein, so the chance of these tomatoes triggering food allergies is extremely small.
  • However, these fruits do contain altered DNA. As I said in my previous article, one could imagine scenarios in which this could pose a health risk. I also pointed out that this is a theoretical concern, not one that has been proven to occur.
  • In addition, these fruits have been irradiated with high-intensity UVB light for an hour. This converts some of the 7-dehydrocholesterol to vitamin D3. But what else does it do to the fruit? Are some of the changes harmful? The authors didn’t ask.
  • Finally, these fruits don’t just have higher levels of vitamin D3. They also have much higher levels of 7-dehydrocholesterol than normal tomatoes. In humans, 7-dehydrocholesterol is made in the skin epidermis and there is very little in other tissues.

Is dietary 7-dehydrocholesterol a problem? We don’t know. One recent study speculated that dietary 7-dehydrocholesterol may increase the risk of atherosclerotic cardiovascular disease more than dietary cholesterol. Perhaps more study is required before we assume that this genetic modification is only beneficial.

   2) Are there environmental risks?

  • The same genetic change that increases the 7-dehydrocholesterol content of the fruit decreases α-tomatine and esculeoside A and B levels. As I stated above, α-tomatine and esculeoside A and B protect tomatoes from fungal, microbial, insect, and herbivoral attack (In my yard, herbivoral attack would be deer).
  • The authors did not describe how these tomatoes were grown, but I would assume it was in a hothouse. That is customary for studies of newly genetically engineered foods.
  • This raises the question of how pest susceptible these tomatoes would be when cultivated outdoors. Would increased amounts of pesticides and fungicides be needed to raise them? If so, what would the environmental impact be? The authors gave no indication that they had thought about the environmental impact if, in fact, these modified tomatoes were widely grown to solve the vitamin D insufficiency, as they proposed.

3) Is there a risk of cross-pollination?

  • This is a major concern for any genetically modified crop. If the modified gene were easily spread to nearby fields by cross-pollination, it could decease crop diversity and create major problems for organic farmers. Again, the authors gave no indication that they had even thought about this issue.

4) Would these tomatoes be accepted in developed countries?

  • I ask this question because the genetically modified Flavr Savr tomato was introduced in the US in 1996 thumbs down symbolwith much fanfare, only to be withdrawn from the market in 1999 due to lack of consumer demand.
  • And this tomato is both genetically engineered and irradiated. I am guessing most consumers would simply prefer to take a vitamin D3

My overall evaluation. Despite what you may hear from genetic engineering gurus, I would give these genetically engineered tomato fruits a thumbs down. There are too many unresolved questions and concerns to consider them to be a beneficial addition to our food supply.

Tomato Leaves Engineered To Produce Vitamin D3

The Benefit:

Again, the benefit is obvious. As the authors said, most experts consider vitamin D3 superior to vitamin D2, and there are no plant sources of vitamin D3 that can be used to produce vitamin D3 supplements. Leaves from this genetically modified tomato plant could be an inexpensive vegan source of vitamin D3.

My Concerns:

1.  Are there health risks?

  • Despite what the “Chicken Little’s” of the world may have told you, there are no health risks when an individual food ingredient is purified from a genetically modified organism. For example, vitamin D3 purified from these genetically modified tomato leaves will contain no genetic material (DNA), no protein, no UV-damaged molecules, and no 7-dehydrocholesterol. It will be chemically and biologically indistinguishable from vitamin D3 obtained from any other source.

2)  Are there environmental risks?

  • The environmental risks are the same as for the fruit.

3)  Is there a risk of cross-pollination?

  • The risk of cross-pollination is the same as for the fruit.

thumbs up4)  Would this source of vitamin D3 be accepted in developed countries?

  • This should not be a concern. Nutrients from genetically modified microorganisms are widely used in natural supplements. And UVB irradiation is already used in the production of both vitamin D2 and vitamin D3 Any UV-damaged molecules are removed in the final purification steps.

My overall evaluation. I would give the tomato leaves a tentative thumbs up. If the environmental and cross-pollination concerns can be overcome, the leaves could be a valuable vegan source of vitamin D3.

The Bottom Line 

Vitamin D insufficiency is a major problem, both worldwide and in the United States. A group of scientists have attempted to solve this problem by producing a genetically modified tomato plant that produces 7-dehydrocholesterol, which can be converted to vitamin D3 by UVB irradiation.

Plant foods are not generally a good source of vitamin D3. Tomatoes are grown and consumed in over 170 countries. Therefore, the scientists proposed widespread cultivation of this genetically modified tomato plant as a solution to worldwide vitamin D insufficiency.

In addition, the leaves of these genetically modified tomato plants contain more 7-dehydrocholesterol than the fruit. Most experts consider vitamin D3 superior to vitamin D2, and there are no plant sources of vitamin D3. The authors of this study further proposed that the leaves from this genetically modified tomato plant could be an inexpensive vegan source of vitamin D3.

As I have discussed in a previous “Health Tips From The Professor” article, both the benefits and risks of genetically modified foods have been greatly overstated. In this article, I evaluated both the benefits and risks of using the fruit as a plant source of vitamin D3 and the leaves to produce vegan vitamin D3 supplements.

Based on a careful evaluation of benefits and risks I give the genetically modified fruit a thumbs-down. There are simply too many unanswered questions.

On the other hand, I give vegan vitamin D3 supplements produced from the leaves a tentative thumbs up depending on whether environmental and cross-pollination concerns can be overcome.

For more details on this study, read the article above.

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure, or prevent any disease.

Health Tips From The Professor