Niacin

What it is
Pellagra, a human disease with symptoms of dermatitis, diarrhoea and mental disturbance, was first defined in Italy two hundred years ago. However it was not until 1915 that it was recognised as a nutritional deficiency and it was 11 more years before yeast was successfully used as a treatment. Nicotinic acid was first synthesised in 1867 and was known to be naturally occurring after it was extracted from rice polishing in 1914. Finally, in 1937, nicotinic acid was shown to be the pellagra-preventing factor. Many more functions of nicotinic acid are now known but the original name -- vitamin PP, (pellagra-prevention) still persists.

At least two chemical products, nicotinic acid and nicotinamide, have similar activities and are grouped as niacin. Both are derivatives of pyrimidine with the addition of either a carboxylic acid or an amide radical. Generally speaking, nicotinic acid is the main source of niacin activity in plant tissues whereas animal tissues contain nicotinamide. Nicotinic acid is readily absorbed from the small intestine into the blood stream of animals. Nicotinamide is thought to lose its amide group in the duodenum and be changed to the acid before absorption. Once absorbed, nicotinic acid is built into a mononucleotide, then to a dinucleotide and finally an amide group is added to form the active enzyme which is transported to muscles and liver where some is stored.
It is also sometimes called vitamin B3.


What it does
Niacin, after being built into an enzyme form, is the active group in two important coenzymes -- nicotinamide adenine dinucleotide (NAD), also known as co-dehydrase I (CoI) and nicotinamide adenine dinucleotide phosphate (NADP) which is co-dehydrase II (CoII). Both these coenzymes catalyse the transfer of hydrogen in the metabolism of proteins, fats and carbohydrates. These activities form part of both breaking-down and building-up processes. For example, they are used repeatedly in the formation of dehydrogenases required in the citric acid (Kreb’s) cycle which releases energy from carbohydrates and other dietary components.


If too much is given
Extremely high intakes greater than 350 mg/kg liveweight have been shown to produce a range of conditions such as increased heart beat, increased respiration rate leading to respiratory paralysis, fatty liver conditions, inhibition of growth and even death in extreme cases. However, such intakes are so far beyond the normal feeding ranges that these effects are of academic interest only and have not been seen in horses. Generally, any excess niacin is rapidly excreted; the normal loss rate is one third of intake excreted within 24 hours. It is worth noting that a few people are allergic to nicotinic acid and develop contact dermatitis.


Biosynthesis
There are two ways in which animals may produce niacin independently from the dietary supply. One possibility is microbial synthesis in the caecum and colon and the other is by conversion of the amino acid tryptophan. The relationship between tryptophan and niacin has been studied extensively. The utilisation rate of tryptophan is rather poor. Primarily it is limited by the dietary supply, which is unlikely to be abundant, and by the absence of sufficient riboflavin and vitamin B6 to catalyse the reaction. Tests have shown that even under perfect conditions the production of 1 g niacin requires 45 g tryptophan. High fat diets appear to suppress the conversion of tryptophan to niacin, with saturated fats having the greatest influence.

Niacin biosynthesis by the microbial population of the caecum and large intestine may not benefit the horse to any major extent because there is little absorption beyond this point.


How it is measured
Chemical assays of mixed feeds must measure the contents of nicotinic acid and nicotinamide if they are to give a true reading of niacin activity. Early methods utilised the Konig reaction with cyanogen bromide which breaks the carbon-nitrogen linkage to the pyridine ring. The subsequent reaction with an aromatic amine can be determined colourimetrically. Direct determination by HPLC is now regarded as a cleaner, safer method. The niacin is extracted by a mixture of water and methanol and the separate peaks of nicotinic acid and nicotinamide measured by UV or fluorimetric detectors.
Unfortunately all assay methods determine total niacin activity; no allowance is made for biological availability. Although niacin can be found in all feeds horses are unlikely to be able to benefit from the total amount present. As a rough guide it should be assumed that only 50% of the niacin calculated or found to be present in a cereal-based feed is of benefit.


Assessment of status
The niacin concentrations in blood plasma or liver are not reliable parameters of niacin status. There has been some work with humans on measuring the excretion of niacin metabolites. The most promising indication of status seems to be the ratio of the excretion of 2-pyridone compared to N-methylnicotinamide. The normal ratio lies between 1.3:1 and 4:1 but as niacin depletion occurs the 2-pyridone excretion rate reduces to zero long before changes occur in N-methylnicotinamide; excretion falls to a minimum at the same time as clinical signs of deficiency appear. Unfortunately, the assay of 2-pyridone is tedious and time-consuming so a simple estimation of N-methylnicotinamide has been more widely used in surveys. There is no information at present whether horses exhibit the same pattern of excretion.


Binding and antagonism
There is ample evidence that a considerable part of the niacin in cereals and oilseed residues is present in an organically-bound form which is very poorly utilised. The niacin in maize, rice and wheat, for example, is only about one third available.

There are some chemical antagonists such as pyridine-3-sulphonic acid and 6-aminonicotinamide but these are not often found in feedstuffs. The amino acid leucine is also an antagonist if present in above average quantities.


Relationships with other ingredients
Many of the vitamins of the B-complex work closely together in metabolism. They may have a sparing action or increase the requirements, depending on individual functions.
Thiamine, riboflavin, vitamin B6, pantothenic acid, folic acid and vitamin B12 all have sparing and synergistic actions on niacin in carbohydrate metabolism and in alleviating deficiencies. In addition, thiamine, riboflavin and vitamin B6 are required for the conversion of tryptophan to niacin and a shortage of any one of these can prevent it. Also the recycling of NAD and NADP require flavoproteins which are dependent on riboflavin.


Requirements and allowances
Requirements are always determined in terms of available niacin. These must be viewed in the context of the levels of protein and of specific amino acids in the ration. Increased levels of protein increase niacin requirements, so do increased contents of leucine; excess tryptophan reduces the requirement. Horses appear to require less niacin than many other animal species.

The following list of proposed feed supplements assumes that compounded rations contain at least 40% cereals or cereal by-products where the biological availability of the naturally occurring niacin is about one third of the total content. It has also been assumed that the amount of tryptophan is not excessive. These figures require amendment for other circumstances.

    mg / kg   mg / day
Adult performance horses in training  
10
  100
Adult performance horses in light work   10   60
Ponies, hacks & hunters   10   30
Mares & stallions   10   40
Young horses 1-2 years   12   36
Foals & yearlings less than 1 year   15   15-60


Stability
Niacin is one of the most stable of all the vitamins. It is virtually unaffected by heat, light, moisture, acids, alkalis or oxidising agents. However, it is unstable in the presence of reducing agents. Nicotinic acid is sparingly soluble in water (1 g in 100 ml at 20°C) whereas nicotinamide is very soluble (1 g in 1ml). Both products are slightly soluble in ethanol and methanol. Feed supplements do not require any extra allowances for processing losses because niacin is stable in feed production.


Livestock conditions suggesting further needs
Since many of the early niacin deficiency symptoms are non-specific and similar to deficiencies of other B-group vitamins, it is always worth trying increased dietary inputs of all the B-vitamins when animal growth or performance are below expectations. However it seems unlikely that horses benefit from additional supplies of niacin above the normal recommended levels.