This means that for each vitamin dependency, there is a dose which can overcome (at least partly) the Inborn Error of Metabolism behind the vitamin dependency and restore cellular chemistry closer to optimal.
Dose dependency thus indicates that to get specific benefits of the nutrient, specific doses, higher than the RDA's, are needed.
Whether it be the limit of how much of a vitamin or mineral the body can absorb or the limit of how much of the vitamin or mineral that the body can actually use (metabolize), the benefits of all nutrients appear to be dose dependent. So while the RDA's do provide nutritional benefits, they do not provide the benefits of higher potencies.
Over the past three decades, orthomolecular doctors have been compiling information about the dose dependencies for each vitamin and mineral. Their major work was to find those levels of potencies that would overcome the Inborn Error of Metabolism involved.
They regarded the most effective doses as those that give the most benefits for the least amount of supplementation. These are called optimal doses.
Over these three decades, in addition to the work of orthomolecular doctors, other scientists and doctors from many fields of research have looked at the nutritional and therapeutic benefits of vitamin and minerals. Today there are over 200,000 studies in the National Public Library of Medicine showing the benefits of USP-type vitamins, minerals and other nutrients, and there are approximately 22,000 studies specifically showing dose dependencies of various benefits from vitamins and minerals.
Dose Dependency Is True For All Nutrients
It's important to note that when a nutrient gives a certain benefit at doses above the RDA, this represents a dose dependent situation. Science is continually looking at dosages and effectiveness and adding to the sum of information about dose dependencies.
As we review the various dosages of various nutrients which give various benefits, it becomes clear that all nutrients have dose dependencies. While it is not yet possible to determine all the dose dependent benefits of vitamin, minerals and other nutrients, modern research has discovered many.
Further, nutrients generally offer a series of different benefits which may progressively appear as the dosages increase until the maximum benefits have appeared.
REVIEW OF DOSE DEPENDENCY SCIENTIFIC STUDIES
Below is a review of a few of the thousands of studies that show a clear dose-dependent beneficial effect for USP-type nutrients. Appropriate doses provide optimal benefits.
1. EXAMPLES OF VITAMIN E DOSE DEPENDENCY
Note: Increased rates of oxidation and lipid peroxidations are thought to be involved in many of the major diseases, like heart disease. Vitamin E is one of the body's main protectors against increased oxidation rates.
Dose dependency of Vitamin E in slowing oxidation rates:
An Australian study in 1996 showed that Vitamin E slows oxidation rates in a dose dependent manner.
- 500 IU per day slowed oxidation 4%
- 1000 IU per day slowed oxidation 19%
- 1500 IU per day slowed oxidation 25%
Simons LA et al. What dose of Vitamin E is required to reduce susceptibility of LDL to oxidation? Australia and New Zealand Journal of Medicine 1996 Aug;26(4):496-503
Dose dependency of Vitamin E for lowering LDL oxidation rates:
Two studies from the University of Texas study showed that increasing doses of Vitamin E progressively lowered oxidative susceptibility of LDL.
Looking at conjugated dienes,
- At 60 IU of vitamin E, oxidation rates did not change
- At 200 IU of vitamin E, oxidation rates slowed 14%
- At 400 IU of vitamin E, oxidation rates slowed 25%
- At 800 IU of vitamin E, oxidation rates slowed 58%
- At 1200 IU of vitamin E, oxidation rates slowed 61%
JJialal I, et al. The effect of alpha-tocopherol supplementation of LDL oxidation. A dose-response study. Arteriosclerosis, Thrombosis, and Vascular Biology 1995 Feb;15(2):190-198
Fuller CJ et al. Effects of increasing doses of alpha-tocopherol in providing protection of low-density lipoprotein from oxidation. American Journal of Cardiology 1998 Jan 15; 81(2):232-3
Dose dependency of Vitamin E and protection from lipid peroxidation:
A 1996 animal study from Spain showed that protection from lipid peroxidation by Vitamin E did not occur at the equivalent of the minimum daily requirement of vitamin E (30 IU) but at six times the daily minimum daily requirement (180-200 IU), a strong protection capacity was obtained.
Rojas C et al. Increase in heart glutathione redox ratio and total antioxidant capacity and decrease in lipid peroxidation after vitamin E dietary supplementation in guinea pigs. Free Radical Biology & Medicine 1996;21(7):907-15
Dose dependency of Vitamin E on maintaining artery wall health:
A study of 600 people showed that doses of vitamin E below 400 IU per day were not effective in maintaining artery wall health, while vitamin E doses from 400 IU to 1,500 IU were beneficial.
Dwyer et al. American Heart Association 41st Annual Conference on Cardiovascular Disease Epidemiology and Prevention, March 8, 2001
2. EXAMPLES OF VITAMIN C DOSE DEPENDENCY
Circulation
Dose dependency of vitamin C to stop decreased blood circulation after smoking:
A 1999 Swedish study showed that 2000 mg of vitamin C can reduce by 40%-50%, the typical reduction in blood circulation that occurs while smoking but that 1000 mg of vitamin C had no effect.
Zhang J et al. A single high dose of vitamin C counteracts the acute negative effect of microcirculation induced by smoking a cigarette. Microvascular Research 1999 Nov;58(3):305-11
Cataracts
Dose dependency of vitamin C on the risk of cataracts:
Another study showed that 294 mg per day of vitamin C significantly decreases the risk of cataracts compared to 77 mg per day.
Clinical Chemistry 39:1305, 1993
Bone Density
Dose dependency of vitamin C on maintaining bone density:
A three-year study showed that women who took between 1,000 mg and 5,000 mg of supplemental USP-type vitamin C per day had 5% greater spinal bone density than women who took 500 mg or less.
Morton DJ, et al. Vitamin C supplement use and bone mineral density in postmenopausal women. Journal of Bone and Mineral Research (US), Jan 2001;16(1):135-40.]
Cold Symptoms
Dose dependency of vitamin C and suppression symptoms of a cold:
Another peer-reviewed study stated that vitamin C doses of 250 mg to 500 mg per day produced no effect on reduction of cold symptoms, while doses from 1,000 mg to 6,000 mg per day decreased the duration of colds by an average of 21%.
Hemila H, et al. Vitamin C and the common cold: a retrospective analysis of Chalmers' review. Journal of the American College of Nutrition1995;14(2):116-123.
3. EXAMPLE OF FOLIC ACID DOSE DEPENDENCY
Birth Defects
Dose dependency of folic acid on preventing neural tube birth defects:
This study stated that the incidence of birth defects (neural tube defects) is about 1.3 cases per 1,000 live births. It also stated that doses of supplemental folic acid could reduce this birth defect by 40% at 400 mcg, and reduce it by 75% at 4,000 mcg. There was a clear higher dose-dependent effect on the reduction of birth defects.
Garcia-Morales MA, et al. Peri-conception use of folic acid in the prevention of neural tube defect: current concepts. Ginecologia y Obstetricia de Mexico 1996 Sep;64:418-421
4. EXAMPLE OF VITAMIN B-6 DOSE DEPENDENCY
PMS
Dose dependency of vitamin B-6 on reducing premenstrual symptoms:
A study of 630 women showed a dose dependent relationship of daily intake of vitamin B-6 and reducing premenstrual symptoms.
- 40 mg of vitamin B-6 produced no significant benefit
- 100-115 mg of vitamin B-6 reduced PMS symptoms in about 66% of the women
- 160-200 mg of vitamin B-6 reduced PMS symptoms in about 79% of the women
Brush MG, et al. Pyridoxine in the treatment of premenstrual syndrome: a retrospective survey in 630 patients, British Journal of Clinical Practice 1988;142(11):448-4562.)
5. EXAMPLES OF CALCIUM DOSE DEPENDENCY
Bone Density
Dose dependency of calcium on maintaining and increasing bone density:
A two-year placebo-controlled study of three groups of senior women showed that those who received 1,000 mg supplemental USP-type calcium carbonate per day added to the 683 mg of food-calcium from their diet (total=1,683 mg of calcium per day) ended the study with 4.8% greater bone density than women who received only 683 mg of food-calcium from their diet.
The group that received only 683 mg of food calcium per day from their diet lost 3% of their greater bone density. The group that received 683 mg of food calcium per day from their diet plus four glasses of milk (total calcium intake 1028 mg) lost 1.5% of their greater bone density. But the group that received a total of 1,683 mg of daily calcium from their diet plus calcium carbonate, "suffered no bone loss and gained significant increase in spinal (3.7%) and hip (3%) bone mineral density." Hip bone density with calcium carbonate was 4.8% greater than with diet alone.
Storm D, et al. Calcium supplementation prevents seasonal bone loss and changes in biochemical markers of bone turnover in elderly New England women: a randomized placebo-controlled trial. Clinics in Endocrinology and Metabolism, 83(11):3817-25 1998
Bone Density and Risk of Fracture
Dose dependency of calcium on bone density and reduced risk of fracture:
Another study of senior women and men, 65 or older, stated that lower calcium doses were not effective to reduce bone loss and reduce the risk of fracture, because they are "...substantially lower than (calcium intake) that human physiology is adapted to by evolution"....".Supplemented intakes (of calcium) of 1300 to 1700 mg per day have been shown to arrest age related bone loss and to reduce fracture risk in people 65 and older."
Heaney RP. Calcium needs of the elderly to reduce fracture risk. Journal of the American College of Nutrition 2001 Apr;20(2 Suppl):192S-197S.
6. MULTIVITAMINS
Dose dependency of multi-vitamins and improved mood, sleep, reaction times:
A double-blind, placebo-controlled study of 129 students over one year showed that those who took a multivitamin with 10 times the RDA of vitamins B1, B2, B3, B6, B12, biotin, vitamin C and vitamin E, had better reaction times, better mood, more restful sleep, and described themselves as more agreeable and better composed. The improvement in mood was most associated with improved riboflavin (vitamin B2) and pyridoxine (vitamin B6) status.
Benton D, et al. Vitamin supplementation for 1 year improves mood. Neuropsychobiology (Switzerland), 1995, 32(2) p98-105
Together, these few examples indicate that all the vitamins, essential minerals and other nutrients are almost surely dose dependent to some degree. This means that the summation of the studies indicates that benefits from nutrients increase with the potency up to a peak (maximum) effect after which there is either no more effect or that an overdose effect may start to happen.
This overdose effect is very rare for vitamins, essential minerals and other nutrients normal to the human body. The U.S. Government Center for Disease Control has no record of anyone dying of a vitamin or an essential mineral (except for the few small children a year who unfortunately eat {sugar coated?} tablets with iron in them). Apparently, vitamins are the safest things we can put in our mouths.
As science and medicine continue to add to this store of knowledge about dose dependency and individual vitamin and mineral dependencies, modern nutrition will continue to become a better tool for protecting and extending our healthy, functional life span.
Orthomolecular Multivitamins Contain Dose-Dependent Levels Of Vitamins:
Orthomolecular nutrition multivitamin formulas include the optimal doses (dose dependent levels) that orthomolecular doctors and nutritionists as well as research scientists have discovered for vitamins, minerals and many other nutrients. These orthomolecular multivitamin formulas therefore bring with them many benefits not available to the lower potency RDA-type multivitamins, and this is why their effectiveness is much higher than multivitamins with merely the RDA levels of vitamins and minerals.
