The Vitamin Paradox

Significant amounts of research have shown many disease states to be associated with multiple vitamin deficiencies; but supplementation and fortification of foods with vitamins has been shown to have made things worse and not better.

Concept

Farming practices, food processing techniques and dietary choices has led to nutrient deficiencies in much of the population.

These nutrient deficiencies are well documented and there have been many initiatives implemented to correct these nutrient deficiencies.

  • Education on food choices e.g. spinach (pop eye) and the food pyramid
  • Food fortification
  • Supplementation

The concept of supplementing with synthetic versions of vitamins without their natural variations in forms and cofactors does not make sense. The thought of simply supplementing with synthetic chemicals that are in many cases not even found in nature because our food is weak in other natural chemicals has turned out to be potentially disastrous.

We need to improve the nutrient levels in foods to correct the nutrient deficiencies in foods and then we need to preserve these nutrients long enough to eat them and then we need to make the right food choices to actually eat them.

More emphasis needs to be placed on the need to improve farming practices, food processing and dietary choices to improve nutrient content of our diets and correct nutrient deficiencies.

History of synthetic vitamins versus nature

The term vitamin was first discovered by Funk. Funk identified that the anti-beriberi substance in unpolished rice was an amine which is a type of nitrogen containing compound. He coined the term “vitamine”; a combination word from vita and amine, meaning amine of life and considered that amines are vital for the life.

Vitamins are required in tiny amounts because of their inactivation in the body they play a catalytic role in many metabolic reactions of the cells and act as coenzymes or part of coenzymes and enzyme systems. Certain vitamins act as hormones and exert their action at intracellular receptor sites like Vitamin A and D.

Market acceptance and education

    • Testing methods
      • E.g. multiple forms of natural folates found in plants but once dissolved in water to test they are hydrolysed and form folic acid and folic acid is then tested for to give an indication of natural folates found in food
    • Standardization of extracts
      • E.g. a plant supplying all forms of natural folates is then standardized to supply a certain amount of folates per gram and this is shown as folic acid mcg / gram on the CofA
    • Labelling and standardization
      • E.g. when an extract was labelled the standardization was included to show the strength of ingredient added. This resulted in folic acid at a certain dose per serve labelled. To compare one product to another product people would compare the levels of folic acid and look at the one with a higher value as the stronger and therefore the superior product.
    • The market was trained over time to look for and compare the “markers” of standardization as the “active ingredient” and to be the point of comparison.
    • Synthetic versions of the “marker of standardization” were then created in labs very cheap compared to growing or sourcing plant material, making an extract from the full plant ort parts of the plant and then testing the extraction to isolate the marker for standardization and adding the larger amount of the extract showing the levels of the standardization marker on the label. Because levels of vitamins vary significantly over the seasons and with varying farming and processing techniques the input amount of the natural plant extract would vary from batch to batch. When you take all of this into consideration you can see why companies would be tempted to simply make a consistent strength and cheap synthetic version of vitamins and just add that instead of going through all of the extra work and expense.

How good intentions can turn bad – Vitamin poisoning

The Obesity Paradox

obesity

The above diagram Jeff discussed was taken from the “Statistics Related to Overweight and Obesity”. CDC. 2006. Retrieved 2009-01-23.

We then discussed the article by Zhou et al “Vitamin Paradox in obesity: Deficiency or excess?” published in the World Journal of Diabetes in August 2015.

Obesity is associated with deficiencies of many vitamins in particular folic acid and vitamin D; paradoxically the introduction of food fortification (B1, B2 and folate) and synthetic vitamin supplements into the diet was followed by a dramatic increase in the prevalence of obesity among all age groups in the United States, Canada, China and Saudi Arabia.

Excess vitamins have three major detrimental effects:

    • (1) increasing ROS generation and subsequently leading to oxidative tissue damage contributing to cardiovascular disease, neurological disorders, insulin resistance (metabolic syndrome, diabetes, obesity);
    • (2) disturbing the degradation of neurotransmitters and hormones by competing for drug metabolizing enzymes and detoxification resources; and
    • (3) causing epigenetic changes (e.g., altered DNA methylation) by depleting the body’s methyl-group pool.

Thus, fortification induced sustained excess vitamin intake may deplete the drug-metabolizing system that is also necessary for controlling detoxification, elimination and conversion of hormones, neurotransmitters, xenoestrogens, pollutants etc. (e.g., manifested by high levels of un-metabolized vitamins) and the antioxidant system, and eventually cause a variety of metabolic disorders and oxidative tissue damage.

This may play a causal role in the increased prevalence of obesity and related diseases, as hypothesized in our previous work

The vitamin paradox in obesity may be a reflection of excess synthetic and unnatural levels of vitamin intake, rather than a vitamin deficiency. Given that there is a correlation between unnatural levels of synthetic vitamin intake and the increased prevalence of obesity, it can be assumed that obesity could be one of the manifestations of chronic vitamin poisoning.

Those suffering with obesity should focus reduce their intake of vitamin-fortified foods and focus on a balanced diet of good quality foods that supply levels of vitamins and minerals in levels and forms as nature intended.

Excretion of vitamins

Water soluble

    • kidneys
    • sweat glands

Fat soluble

    • liver
    • the sebaceous glands excrete lipid-soluble vitamins in the sebum
    • they accumulate in fatty tissue

Water soluble vitamins

Sweating

The efficiency of sweat excretion is determined by several factors, including genetic background, intrauterine and early postnatal development, environmental temperature and physical activity. Compared with whites, blacks have a high sweating threshold, and may have lower sweat excretion of vitamins than whites. Preterm birth is associated not only with a lower renal reserve capacity but also with a low sweating function.

Vitamin levels have increased and sweating decreased over last few decades. Both natural and artificial sources (i.e., vitamin fortification and supplementation) of vitamins have significantly increased, while sweat excretion has significantly decreased due to physical inactivity and the widespread use of air conditioning. These dietary and lifestyle changes may increase the risk of excess accumulation of vitamins in the body, especially in those with reduced excretory capacity and/or activity.

Vitamin degradation / detoxification

Vitamins also undergo degradation through phase  I  (including oxidation, reduction, and hydrolysis) and phase II metabolisms (e.g., sulfation, methylation and glutathione conjugation), which are catalysed by phase  I  and phase II drug-metabolizing enzymes, respectively. After phase  I  and/or phase II degradation, vitamins become more water-soluble and then can be more easily excreted from the body. Excess vitamins are degraded very rapidly.

Vitamins, xenobiotics, neurotransmitters and hormones share the same drug-metabolizing enzyme system, so they may interact with one another in their metabolism by inducing and competing for the enzymes. Phase II metabolism of vitamins consumes detoxification resources, such as methyl-group donors, sulphate donors and glutathione, which are also necessary for the degradation of neurotransmitters and hormones. Therefore, excess vitamins can disturb the phase II metabolism of neurotransmitters and hormones by competing for the limited detoxification resources.

For example:

Niacin

Two large-scale randomized niacin trials (nicotinic acid, 1500-2000 mg/d) show that nicotinic acid has many adverse effects, including loss of glycaemic control among persons with diabetes, new-onset diabetes   and increased risk of death.

Excess vitamins are not needed and are degraded very rapidly. For example, cumulative administration of 2000 mg nicotinic acid [166 times the estimated average daily requirement (EAR)] in 13 h 10 min is found to only increase the levels of its metabolites in the plasma, without significantly changing plasma nicotinic acid concentrations. We found that, at 5 h after oral administration of 100 mg nicotinamide (8.3 times the EAR), plasma nicotinamide had returned to near baseline levels, while its metabolite N1-methylnicotinamide remained at high levels. Thus, it is clear that a transient increase in vitamin intake may not change fasting vitamin levels.

Niacin methylation as a good example to explain how excess vitamins affect metabolism of neurotransmitters and hormones. Since niacin is degraded mainly through methylation, niacin fortification/supplementation (usually using its nicotinamide form) increases the demand for methyl groups on the one hand, and on the other hand, it can overburden and exhaust methylation resources such as choline and betaine. As a result, excess nicotinamide reduces the size of the pool of methylating agents and subsequently inhibits the methylation of endogenous substrates (e.g., catecholamines, estrogens and DNA), leading to an increase in plasma norepinephrine levels, 16 alpha hydroxyl estrone and DNA hypomethylation, an important epigenetic alteration in human diseases.

Grain fortification with Niacin supplies nicotinamide and glucose and this combination can induce insulin resistance due to excess ROS formed from the degradation of niacin and subsequent reactive hypoglycaemia, demonstrating that vitamin-fortified grains can increase appetite and obesity.

Folic acid fortification and supplementation

Folate, an essential micronutrient, is a critical cofactor in one-carbon metabolism. Mammals cannot synthesize folate and depend on supplementation to maintain normal levels.

Low folate status may be caused by

    • low dietary intake,
    • poor absorption of ingested folate Low stomach acid
    • and alteration of folate metabolism due to genetic defects MTHFR gene
    • or drug interactions (methotrexate)

Folate needed for detox of homocysteine, neural tube defects, cancer prevention, estrogen detox (methylation reactions).

Folate is the generic term for a family of compounds including folic acid and its derivatives which include 5- methyltetrahydrofolate (5-MTHF), 5-formyltetrahydrofolate (5-FTHF or folinic acid), 10-formyl-THF, 5,10-methylene- THF and unsubstituted THF.

But a build-up of synthetic unconverted folic acid can increase the risk of cancer, especially breast cancer.

Folic acid is the synthetic, parent compound of this family. It is an oxidized synthetic water-soluble member of the vitamin-B complex family which does not exist in nature, although oxidation of folates to folic acid is seen in stored or cooked foods.

External supplementation of folate may occur as folic acid, folinic acid or 5-methyltetrahydrofolate (5-MTHF). Naturally occurring 5-MTHF has important advantages over synthetic folic acid –

    • it is well absorbed even when gastrointestinal pH is altered and its bioavailability is not affected by metabolic defects.
    • Using 5-MTHF instead of folic acid reduces the potential for masking haematological symptoms of vitamin B12 deficiency, (B12 is needed for MTHFR and interestingly B12 injections can also mask folate deficiency)
    • Bypasses MTHFR polymorphism
    • Use of 5-MTHF also prevents the potential negative effects of unconverted folic acid in the peripheral circulation.

Fat soluble vitamin overload

There is a cool article by Ravisankar et al “The Comprehensive Review on Fat Soluble Vitamins” published in November 2015 in IOSR Journal of Pharmacology.

Fat-soluble means that these vitamins are transported with fat and stored in the liver and fat tissue or eliminated via sebum in skin. Because they can be stored, they can build up and become toxic when eaten in excessive amounts. This mostly occurs when taking single supplements of the fat-soluble vitamins rather than in foods rich in vitamins. Eating fat-free can lead to health problems can lead to vitamin deficiencies.

Vitamin A

A vitamin is two types. 1. Preformed vitamin A is found in the form of retinol and is the most usable form of the vitamin. You can find preformed vitamin A in your everyday diet in animal products like whole milk, liver, and eggs. 2. Provitamin A is found in the form of carotenoids and is converted in part into retinol. Beta-carotene, alpha-carotene, and betacryptoxanthin are the most common carotenoids, with beta-carotene being the most easily converted into retinol. Beta-carotene is found naturally in many fruits and vegetables like peaches and carrots.

Colon cancer. Research shows that taking beta-carotene by mouth, alone or with vitamins C and E, selenium, and calcium carbonate, does not decrease the risk of colon tumor growth. In some people who have had colon tumors removed, taking beta-carotene supplements seems to reduce the risk of recurrence. However, in people that smoke cigarettes and drink alcohol, taking beta-carotene supplements increases the risk of new tumors. It is unclear if dietary beta-carotene reduces the risk of colon cancer.

Lung cancer. Taking beta-carotene actually seems to increase the risk of lung cancer in people who smoke (especially those smoking more than 20 cigarettes per day), former smokers, people exposed to asbestos, and those who use alcohol (one or more drinks per day) in addition to smoking. However, beta-carotene from food does not seem to have this adverse effect. Also, taking supplements containing beta-carotene, vitamin E, and selenium for about 5 years does not reduce the risk of death in people previously diagnosed with lung cancer.

Prostate cancer. Taking beta-carotene supplements does not prevent prostate cancer in most men. In fact, there is some concern that beta-carotene supplements might actually increase the risk of prostate cancer in some men. There is evidence that men who take a multivitamin daily along with a separate beta-carotene supplement have an increased risk of developing advanced prostate cancer. Also, men who smoke and take beta-carotene supplements have in increased risk of developing prostate cancer.

Vitamin E:

Thus, the natural vitamin E exists in 8 different forms. The 4 forms of tocopherols and the tocotrienols are like alpha (α), beta (β), gamma (γ) and delta (δ) forms. Amongst these, α-tocopherol is the most copious and highly active form.

Vitamin E is the anti-sterility factor which is essential for fertility of the male and the birth process of the female.

Vitamin E and C can scavenge ROS via activation of the endogenous glutathione antioxidant system, by which vitamin C and vitamin E are recycled. The endogenous glutathione antioxidant system maintains vitamin C and vitamin E recycling and actually determines the antioxidant effect of these vitamins.

High levels of supplementation of vitamin C and vitamin E are not only unnecessary but may be harmful due to increasing the burden of the glutathione antioxidant system. It is obvious that excess vitamin intake may provide an additional source of ROS.

It is not surprising that some randomized clinical trials show that high-dosage supplementation vitamin E 400iu over long periods of time may increase, rather than decrease, cardiovascular events and all-cause mortality. Increased risk of death. Intensive studies reveal that people who take doses of more than 400 international units (IU) per day produces an increased risk of death along with all causes combined.

Vitamin D

Vitamin D is synthesized in the body by irradiation of sterols in the skin by UV rays.

Nutritionally important two forms of vitamin D are vitamin D2 (ergocalciferol) which is found in plants and vitamin D3 (cholecalciferol) is synthesized in the body from cholesterol.

Many studies have examined the effect of Vitamin D supplementation on the disorders, including obesity, diabetes, hypertension, dyslipidemia, cardiovascular disease, cancer, depression, and asthma. Unfortunately, most, if not all, of published meta-analyses have failed to show a significant benefit of vitamin D supplementation with or without calcium. It is likely that low fasting serum 25-hydroxyvitamin D status may be not the cause of these diseases.

The skin is a major determinant of 25-hydroxyvitamin D status. Besides synthesizing vitamin D, the skin also functions as a powerful excretory organ. Notably, the skin functions fluctuate with seasonal temperature fluctuation, with the highest activities in summer and lowest activities in winter. Thus, it is likely that decreased skin excretory function may be a cause of human diseases. E.g For example, sebum excretion decreases in winter and inhibition of sebum excretion increases the levels of blood triglycerides and cholesterol.

Interestingly, there is a graded relationship between vitamin D status and body mass index. Sadiya et al found that it is difficult to achieve target levels of 25-hydroxyvitamin D above 75 nmol/L in type 2 diabetic obese subjects with a relatively high daily dose of vitamin D3. Recently, Didriksen et al performed a 5-year intervention study with vitamin D3 at a dose of 20000 IU (500 μg) per week vs placebo in subjects with impaired glucose tolerance and/or impaired fasting glucose, and they found that those given vitamin D3 had significantly higher vitamin D concentration in their adipose tissue (about 6.5 times the placebo group), while their median serum 25-hydroxyvitamin D level only increased from the baseline of 61 to 99 nmol/L. This study clearly demonstrates that large amounts of vitamin D3 are stored in adipose tissue after vitamin D3 supplementation, and suggests that overweight and obese subjects may store more vitamin D than normal weight subjects because they have larger amounts of adipose tissue.

Vitamin K

In the twenty-first century its role in preventing calcification of the blood vessels and other soft tissues became clear. Vitamin K2, found in animal fats and fermented foods, in leafy greens and in much smaller quantities in most diets when compared to vitamin K1. Vitamin K1 more effectively supports blood clotting, while vitamin K2 is also essential for building strong bones, preventing heart disease, and it plays a crucial part in other bodily processes as well. The biological role of vitamin K2 help to move calcium into the proper areas in the body, such as bones and teeth and also helps to remove calcium from arteries and soft tissues.

Out of two types of vitamin K, one is found in plants, and other is found in bacteria.

Plants make phylloquinone (vitamin K1) and bacteria make a number of forms of the vitamin called menaquinone. The bacterial forms are collectively called vitamin K2.

GMO Foods

A GMO or genetically modified organism is created by merging the DNA from different species to create an organism; plant, animal, bacteria or virus which cannot be produced in nature or through traditional crossbreeding. It can bring about the production of foods that taste better, have longer shelf lives, or withstand harsh growing conditions.

  1. GMOs are unhealthy: Since the introduction of GMOs in the mid-1990s, the number of food allergies has sky-rocketed, and health issues such as autism, digestive problems and reproductive disorders are on the rise. Animal testing with GMOs has resulted in cases of organ failure, digestive disorders, infertility and accelerated aging. Despite an announcement in 2012 by the American Medical Association stating they saw no reason for labeling genetically modified foods,the American Academy of Environmental Medicine has urged doctors to prescribe non-GMO diets for their patients.
  2. They increase herbicide use: Monsanto came up with the idea for Round-up Ready crops, the theory was to make the crops resistant to the pesticide that would normally kill them. This meant the farmers could spray the crops, killing the surrounding weeds and pests without doing any harm to the crops themselves. However, after a number of years have passed, many weeds and pests have themselves become resistant to the spray, and herbicide-use increased (both in amount and strength) by 11% between 1996 and 2011. Which translates to – lots more pesticide residue in our foods – yum!
  3. They are everywhere! GMOs make up about 70-80% of our foods in the United States. Most foods that contain GMOs are processed foods. But they also exist in the form of fresh vegetables such as corn on the cob, papaya and squash. The prize for the top two most genetically modified crops in the United States goes to corn and soy. Think about how many foods in your pantry or refrigerator contain corn or its byproducts (high fructose corn syrup) or soy and its byproducts (partially hydrogenated soybean oil).
  4. GM crops don’t ensure larger harvests. As it turns out, GMO crop yields are not as promising as some projections implied. In fact, in some instances, they have been out-yielded by their non-GMO counterparts. This conclusion was reached in a 20 year study carried out by the University of Wisconsin and funded by the U.S. Department of Agriculture. Thus negating one of the main arguments in favor of GMOs.

Synthetic Vitamin A – Synthetic vitamin A is made from combining fish or palm oil with beta-ionone. Palm oil is leading to deforestation of rainforest and endangerment of orangutans.

Synthetic Vitamin B1 – Thiamine mono-nitrate or thiamine hydro-chloride is made from coal tar, ammonia, acetone, and hydrochloric acid

Synthetic Vitamin B2 – Synthetic riboflavin is made with a-cetic acid and nitrogen or using genetically modified bacteria

Synthetic Vitamin B3 – Nico-tinic acid is created using coal tar, ammonia, acids, 3-cyan-o-pyri-dine, and formaldehyde

 Synthetic Vitamin B6 – Pyri-doxine hydrochloride comes from petroleum ester, hydrochloric acid, and formaldehyde. It isn’t readily absorbed or converted and has been shown to inhibit the action of natural B6 in the body

 Synthetic Vitamin B9 – Folic acid doesn’t exist in natural foods, is crystalline, and is not easily absorbed despite the large amounts that are added to vitamins and supplements. It comes from petroleum derivatives

Synthetic Vitamin B12 – Cobalt and cyanide are fermented to make cyanocobalamin

 Synthetic Vitamin C – Ascorbic acid is an isolated vitamin from genetically modified corn sugar that is hydrogenated and processed with acetone- Bioflavonoids = none!

Vitamin D – Natural sources are. Mushrooms, yeast, and lichen produce vitamin D when exposed to sunlight. Humans do too. A daily dose of about 20 minutes of sunlight provides all we need. Vitamin D3 is the most effective kind, the same that comes from our own skin and lichen. Mushrooms and yeast often yield D2. Synthetic Vitamin D – To mimic the natural production we find in our skin, scientists irradiate animal fat to stimulate vitamin D3 synthesis

 Synthetic Vitamin K – Synthetic vitamin K, menadione, comes from coal tar derivatives and genetically modified and hydrogenated soybean oil, and uses hydrochloric acid and nickel. It is considered highly toxic and damages the immune system.